Open AccessHigh aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability
Author(s) -
Croker Alysha K.,
Goodale David,
Chu Jenny,
Postenka Carl,
Hedley Benjamin D.,
Hess David A.,
Allan Alison L.
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00455.x
Subject(s) - cd44 , cancer stem cell , metastasis , aldehyde dehydrogenase , cancer research , stem cell , cd24 , stem cell marker , cancer , cancer cell , biology , cell , pathology , medicine , microbiology and biotechnology , biochemistry , enzyme , genetics
Cancer stem cells (CSCs) have recently been identified in leukaemia and solid tumours; however, the role of CSCs in metastasis remains poorly understood. This dearth of knowledge about CSCs and metastasis is due largely to technical challenges associated with the use of primary human cancer cells in pre‐clinical models of metastasis. Therefore, the objective of this study was to develop suitable pre‐clinical model systems for studying stem‐like cells in breast cancer metastasis, and to test the hypothesis that stem‐like cells play a key role in metastatic behaviour. We assessed four different human breast cancer cell lines (MDA‐MB‐435, MDA‐MB‐231, MDA‐MB‐468, MCF‐7) for expression of prospective CSC markers CD44/CD24 and CD133, and for functional activity of aldehyde dehydrogenase (ALDH), an enzyme involved in stem cell self‐protection. We then used fluorescence‐activated cell sorting and functional assays to characterize differences in malignant/metastatic behaviour in vitro (proliferation, colony‐forming ability, adhesion, migration, invasion) and in vivo (tumorigenicity and metastasis). Sub‐populations of cells demonstrating stem‐cell‐like characteristics (high expression of CSC markers and/or high ALDH) were identified in all cell lines except MCF‐7. When isolated and compared to ALDH low CD44 low/– cells, ALDH hi CD44 + CD24 − (MDA‐MB‐231) and ALDH hi CD44 + CD133 + (MDA‐MB‐468) cells demonstrated increased growth ( P < 0.05), colony formation ( P < 0.05), adhesion ( P < 0.001), migration ( P < 0.001) and invasion ( P < 0.001). Furthermore, following tail vein or mammary fat pad injection of NOD/SCID/IL2γ receptor null mice, ALDH hi CD44 + CD24 − and ALDH hi CD44 + CD133 + cells showed enhanced tumorigenicity and metastasis relative to ALDH low CD44 low/– cells ( P < 0.05). These novel results suggest that stem‐like ALDH hi CD44 + CD24 − and ALDH hi CD44 + CD133 + cells may be important mediators of breast cancer metastasis.